The use of self-reported symptoms as a proxy for acute organophosphate poisoning after exposure to chlorpyrifos 50% plus cypermethrin 5% among Nepali farmers:a randomized, double-blind, placebo-controlled, crossover study

BACKGROUND: Previous studies stating a high prevalence of occupational acute pesticide poisoning in developing countries have mainly relied on measurements of the rather non-specific self-reported acute pesticide poisoning symptoms. Only a few studies have measured the biomarker plasma cholinesterase (PchE) activity, in addition to the symptoms, when assessing occupational acute pesticide poisoning. This study evaluated self-reported symptoms as a proxy for acute organophosphate poisoning among Nepali farmers by examining self-reported acute organophosphate poisoning symptoms and PchE activity in response to occupational acute organophosphate exposure. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover trial among 42 Nepali commercial vegetable farmers. The farmers were randomly assigned (ratio 1:1) to a 2-h organophosphate (chlorpyrifos 50% plus cypermethrin 5%: moderately hazardous) spray session or a 2-h placebo spray session, and after 7 days’ washout, the farmers were assigned to the other spray session. Before and after each spray session farmers were interviewed about acute organophosphate poisoning symptoms and PchE activity was measured. Analyses were conducted with a Two Sample T-test and Mann Whitney U-test. RESULTS: We found no difference in the symptom sum or PchE activity from baseline to follow up among farmers spraying with organophosphate (symptom sum difference −1, p = 0.737; PchE mean difference 0.02 U/mL, p = 0.220), placebo (symptom sum difference 9, p = 0.394; PchE mean difference 0.02 U/mL, p = 0.133), or when comparing organophosphate to placebo (symptom p = 0.378; PchE p = 0.775). However, a high percentage of the farmers reported having one or more symptoms both at baseline and at follow up in the organophosphate spray session (baseline 47.6%, follow up 45.2%) and placebo spray session (baseline 35.7%, follow up 50.0%), and 14.3% of the farmers reported three or more symptoms after the organophosphate spray session as well as after the placebo spray session. CONCLUSION: We found a general presence of acute organophosphate symptoms among the farmers regardless of organophosphate exposure or poisoning. Thus, self-reported acute organophosphate symptoms seem to be a poor proxy for acute organophosphate poisoning as the occurrence of these symptoms is not necessarily associated with acute organophosphate poisoning. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02838303. Registered 19 July 2016. Retrospectively registered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-016-0205-1) contains supplementary material, which is available to authorized users

Micro- and macrovascular complications and risk factors for foot ulceration and amputation in individuals receiving dialysis with and without diabetes

INTRODUCTION: This study examined the prevalence of microvascular and macrovascular complications in people receiving dialysis with and without diabetes and investigated independent risk factors for foot ulcers and lower‐extremity amputations. METHODS: We performed a cross‐sectional study of 119 individuals with diabetes and 219 individuals without diabetes receiving chronic dialysis during June 2019 at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Effects of diabetes and other risk factors were assessed by log‐binomial regression. Prevalence data were compared with a historical control group of 38 individuals with diabetes receiving dialysis examined in 2004 in the same department. RESULTS: We found that persons with diabetes had a twofold higher risk ratio of current (unadjusted risk ratio 2.2 [95% CI 1.1, 4.7]) and previous foot ulcer (2.5 [1.7, 3.7]) and a fourfold higher risk ratio of lower‐extremity amputation (4.2 [2.1, 8.6]) in comparison with persons without diabetes (all p < .05). Furthermore, persons with diabetes had a 70% increased risk ratio of myocardial infarction (1.7 [1.0–2.8], p = .041). In multivariable‐adjusted analysis, current foot ulcer was independently associated with previous foot ulcer (adjusted risk ratio 4.0 [95% CI 1.8, 8.9]), while lower‐extremity amputation was independently associated with diabetes (3.8 [1.8, 8.2]) and male sex (4.1 [1.5, 11.3]) (all p < .01). CONCLUSIONS: Individuals with diabetes receiving dialysis had a higher prevalence of foot ulcer, lower‐extremity amputation and myocardial infarction compared to individuals without diabetes. Previous foot ulcer was the most important risk factor for current foot ulcer, while diabetes and male sex were important risk factors for lower‐extremity amputation

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial

INTRODUCTION: Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit.METHODS AND ANALYSIS: The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient.ETHICS AND DISSEMINATION: The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals.TRIAL REGISTRATION NUMBERS: NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.</p

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial

Introduction Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit.Methods and analysis The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0–3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient.Ethics and dissemination The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals.Trial registration numbers NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00